Genital human papillomavirus (HPV) infection is one of the most common sexually transmitted infections and the principal cause of cervical cancer. The broad goal of this study is to determine the detailed natural history of HPV infection, on a type/subtype specific basis, in a cohort unique for its long follow-up, large size and the fact that it is a truly representative (i.e., population-based) sample of an entire community. Approximately 10,000 women in a high-risk Costa Rican province were enrolled and have been followed approximately 7 years for development of incident high-grade CIN (and rare cancers). During the project, comprehensive repeat screening tests and cervical specimens for HPV DNA testing were obtained. The specific aims of this project are to: (1) describe the detailed natural history of HPV infection on a type-specific and variant-specific basis. The prevalence, incidence and duration of HPV infection and risk factors for persistent infection and progression to high-grade CIN in different age groups will be defined; (2) investigate the elevated prevalence of HPV in postmenopausal women by performing a nested case-control study; (3) identify the genetic basis for the oncogenicity of high-risk HPV types and variants. We hypothesize that natural selection has resulted in the emergence of genetically related cancer-causing HPV types. The complete set of viral genotypes associated with high-grade disease and a set of comparison genomes will be determined and analyzed.